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Cui CQ, Li Z, Hou ZR, Zhang YM, Feng XZ, Tan X, Zhao YY, Li SX, Tian DH, Zhang XY. Relationship between thyroid-stimulating hormone and blood lipids in patients with first-episode depression. BMC Psychiatry 2024; 24:783. [PMID: 39516818 PMCID: PMC11549850 DOI: 10.1186/s12888-024-06168-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 10/14/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Previous studies demonstrated thyroid stimulating hormone (TSH) plays an important role in regulating lipid metabolism, but the relationship between the two is controversial. Meanwhile, it has not been reported in a population with major depressive disorder (MDD). METHODS We divided 1718 first-episode and drug naïve patients with MDD into a TSH abnormal group (TSH-AB) and a TSH normal group (TSH-NOR). The participants in the two groups were assessed by the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the positive subscale of Positive and Negative Syndrome Scale. The patients' blood was tested for TSH, free T3, free T4, fasting blood glucose, lipid indexes and body mass index was recorded. RESULTS The participants in the TSH-AB group had significantly higher HAMD scores, HAMA scores and total scores of positive symptoms, as well as higher incidence of suicide attempts than those in the TSH-NOR group, accompanied by significantly higher thyroglobulin antibodies, thyroid peroxidase antibodies, fasting blood glucose values, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels compared with those of TSH-NOR patients. However, the high-density lipoprotein cholesterol (HDL-C) of TSH-AB patients was lower than those of TSH-NOR patients. TSH values were positively correlated with TC, TG, and LDL-C values, and negatively correlated with HDL-C value. CONCLUSION TSH was highly correlated with abnormal lipid metabolism in patients with MDD. The specific molecular mechanism of the relationship between TSH, lipid metabolism and the development of depression needs to be further in-depth investigation.
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Affiliation(s)
- Chun-Qing Cui
- The Third Honorable Veterans Special Care Hospital, Baoding, 071000, Hebei Province, China
| | - Zhe Li
- School of Government, Beijing Normal University, 19# Xinjiekou Wai Street, Haidian District, Beijing, 100875, China.
| | - Zi-Rong Hou
- Baoding NO.1, Central Hospital, Baoding, 071030, China
| | - Yu-Mei Zhang
- Department of Emergency Medicine, Peking University Third Hospital, Beijing, 100191, China
| | - Xue-Zhu Feng
- National Institute on Drug Dependence and Beijing Key laboratory of Drug Dependence Research, Peking University, Beijing, 100191, China
- Department of Neurobiology, Peking University Health Science Center, Beijing, 100191, China
| | - Xuan Tan
- National Institute on Drug Dependence and Beijing Key laboratory of Drug Dependence Research, Peking University, Beijing, 100191, China
- Department of Neurobiology, Peking University Health Science Center, Beijing, 100191, China
| | - Yu-Yu Zhao
- National Institute on Drug Dependence and Beijing Key laboratory of Drug Dependence Research, Peking University, Beijing, 100191, China
- Department of Neurobiology, Peking University Health Science Center, Beijing, 100191, China
| | - Su-Xia Li
- National Institute on Drug Dependence and Beijing Key laboratory of Drug Dependence Research, Peking University, Beijing, 100191, China
| | - Dong-Hua Tian
- School of Sociology, Beijing Normal University, 19# Xinjiekou Wai Street, Haidian District, Beijing, Beijing, 100875, 100875, China.
| | - Xiang-Yang Zhang
- Hefei Fourth People's Hospital; Anhui Mental Health Center, Affiliated Mental Health Center of Anhui Medical University, 316 Huangshan Road, Shushan District, Hefei, 230022, Anhui Province, China.
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Sublette ME, Daray FM, Ganança L, Shaikh SR. The role of polyunsaturated fatty acids in the neurobiology of major depressive disorder and suicide risk. Mol Psychiatry 2024; 29:269-286. [PMID: 37993501 DOI: 10.1038/s41380-023-02322-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 10/19/2023] [Accepted: 11/07/2023] [Indexed: 11/24/2023]
Abstract
Long-chain polyunsaturated fatty acids (LC-PUFAs) are obtained from diet or derived from essential shorter-chain fatty acids, and are crucial for brain development and functioning. Fundamentally, LC-PUFAs' neurobiological effects derive from their physicochemical characteristics, including length and double bond configuration, which differentiate LC-PUFA species and give rise to functional differences between n(omega)-3 and n-6 LC-PUFAs. LC-PUFA imbalances are implicated in psychiatric disorders, including major depression and suicide risk. Dietary intake and genetic variants in enzymes involved in biosynthesis of LC-PUFAs from shorter chain fatty acids influence LC-PUFA status. Domains impacted by LC-PUFAs include 1) cell signaling, 2) inflammation, and 3) bioenergetics. 1) As major constituents of lipid bilayers, LC-PUFAs are determinants of cell membrane properties of viscosity and order, affecting lipid rafts, which play a role in regulation of membrane-bound proteins involved in cell-cell signaling, including monoaminergic receptors and transporters. 2) The n-3:n-6 LC-PUFA balance profoundly influences inflammation. Generally, metabolic products of n-6 LC-PUFAs (eicosanoids) are pro-inflammatory, while those of n-3 LC-PUFAs (docosanoids) participate in the resolution of inflammation. Additionally, n-3 LC-PUFAs suppress microglial activation and the ensuing proinflammatory cascade. 3) N-3 LC-PUFAs in the inner mitochondrial membrane affect oxidative stress, suppressing production of and scavenging reactive oxygen species (ROS), with neuroprotective benefits. Until now, this wealth of knowledge about LC-PUFA biomechanisms has not been adequately tapped to develop translational studies of LC-PUFA clinical effects in humans. Future studies integrating neurobiological mechanisms with clinical outcomes may suggest ways to identify depressed individuals most likely to respond to n-3 LC-PUFA supplementation, and mechanistic research may generate new treatment strategies.
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Affiliation(s)
- M Elizabeth Sublette
- Department of Psychiatry, Columbia University, New York, NY, USA.
- Molecular Imaging & Neuropathology Area, New York State Psychiatric Institute, New York, NY, USA.
| | - Federico Manuel Daray
- University of Buenos Aires, School of Medicine, Institute of Pharmacology, Buenos Aires, Argentina
- National Scientific and Technical Research Council, Buenos Aires, Argentina
| | - Licínia Ganança
- Clínica Universitária de Psiquiatria e Psicologia Médica, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
- Departamento de Psiquiatria e Saúde Mental, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
| | - Saame Raza Shaikh
- Nutritional Obesity Research Center, Department of Nutrition, Gillings School of Global Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Emekdar G, Taş Hİ, Şehitoğlu H. Investigation of the Relationship between Inflammation and Oxidative Stress Markers and Treatment Response in First-Attack Major Depression Patients: A Follow-Up Study. TURK PSIKIYATRI DERGISI = TURKISH JOURNAL OF PSYCHIATRY 2023; 34:89-99. [PMID: 37357895 PMCID: PMC10552169 DOI: 10.5080/u26698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/27/2023]
Abstract
OBJECTIVE There is a need to biomarkers for major depression (MD). The goals of this study are to compare serum levels of oxidative stress markers malondialdehyde (MDA) and F2-isoprostane and inflammation markers tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) between patients with first-episode MD and healthy controls, to investigate the change of these markers after treatment and to investigate the relationship between levels of these markers and treatment response. METHOD Our study was performed in 30 first-episode MD patients and 30 healthy volunteers. During the clinical evaluation Hamilton Depression Rating Scale and Clinical Global Impression Scale were applied to the participants. Serum levels of markers were measured at the baseline and after 8 weeks of treatment. RESULTS Compared to the control group, first-episode MD patients had significantly higher IL-6, CRP and MDA levels and lower F2- isoprostane levels. There was no difference between the groups in terms of TNF-α levels. TNF-α, IL-6, MDA and F2-isoprostane levels decreased significantly after treatment, whereas there was no significant change in CRP levels with treatment. Baseline F2-isoprostane levels were found to be significantly higher in treatment responders than nonresponders (p<0.05). CONCLUSION In our study, it was shown that there are irregularities related to inflammatory processes and oxidative stress in MD, even in patients who had their first-episode and did not take medication, and these irregularities can be resolved after treatment. While there was a relationship between treatment response and baseline F2-isoprostane levels, there was no relationship with other biomarkers.
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Khantakova JN, Bondar NP, Antontseva EV, Reshetnikov VV. Once induced, it lasts for a long time: the structural and molecular signatures associated with depressive-like behavior after neonatal immune activation. Front Cell Neurosci 2022; 16:1066794. [PMID: 36619667 PMCID: PMC9812963 DOI: 10.3389/fncel.2022.1066794] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 11/29/2022] [Indexed: 12/24/2022] Open
Abstract
Adverse factors such as stress or inflammation in the neonatal period can affect the development of certain brain structures and have negative delayed effects throughout the lifespan of an individual, by reducing cognitive abilities and increasing the risk of psychopathologies. One possible reason for these delayed effects is the neuroinflammation caused by neonatal immune activation (NIA). Neuroinflammation can lead to disturbances of neurotransmission and to reprogramming of astroglial and microglial brain cells; when combined, the two problems can cause changes in the cytoarchitecture of individual regions of the brain. In addition, neuroinflammation may affect the hypothalamic-pituitary-adrenal (HPA) axis and processes of oxidative stress, thereby resulting in higher stress reactivity. In our review, we tried to answer the questions of whether depressive-like behavior develops after NIA in rodents and what the molecular mechanisms associated with these disorders are. Most studies indicate that NIA does not induce depressive-like behavior in a steady state. Nonetheless, adult males (but not females or adolescents of both sexes) with experience of NIA exhibit marked depressive-like behavior when exposed to aversive conditions. Analyses of molecular changes have shown that NIA leads to an increase in the amount of activated microglia and astroglia in the frontal cortex and hippocampus, an increase in oxidative-stress parameters, a change in stress reactivity of the HPA axis, and an imbalance of cytokines in various regions of the brain, but not in blood plasma, thus confirming the local nature of the inflammation. Therefore, NIA causes depressive-like behavior in adult males under aversive testing conditions, which are accompanied by local inflammation and have sex- and age-specific effects.
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Affiliation(s)
- Julia N. Khantakova
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia,Federal Government-Funded Scientific Institution Research Institute of Fundamental and Clinical Immunology (RIFCI), Novosibirsk, Russia,*Correspondence: Julia N. Khantakova
| | - Natalia P. Bondar
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia,Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia
| | - Elena V. Antontseva
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia
| | - Vasiliy V. Reshetnikov
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia,Department of Biotechnology, Sirius University of Science and Technology, Sochi, Russia
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Buculei I, Dobrin ME, Matei D, Onu I, Vicol C, Cioroiu IB, Niculaua M, Iordan DA, Cernomaz A, Trofor AC. Polycyclic Aromatic Hydrocarbons Induced by Smoking and Air Pollution: Correlation with Oxidative Stress in Chronic Obstructive Pulmonary Disease Patients. TOXICS 2022; 10:toxics10110681. [PMID: 36422889 PMCID: PMC9699204 DOI: 10.3390/toxics10110681] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/25/2022] [Accepted: 11/05/2022] [Indexed: 05/28/2023]
Abstract
Oxidative stress is induced by tobacco smoking and is also associated with exposure to air pollution, which are two of the most important risk factors for chronic obstructive pulmonary disease (COPD). The aim of this study was to correlate tobacco use and exposure to air pollution with oxidative stress markers useful in clinical practice in patients with COPD. A total of 102 patients were included and the levels of polycyclic aromatic hydrocarbons (PAHs), malondialdehyde, uric acid and number of packs-years (PY) were determined. Also, six different ratios were used to assess the source of exposure. The results obtained in this study show an admission of pollutants according to smoking status (former smokers/smoker/non-smokers) quantified in average total concentrations for the group of patients with COPD of 4.12 ng/mL, 6.76 ng/mL, 6.04 ng/mL. The six ratios used show that in COPD, the content of PAHs in the blood could be a result of diesel emissions and fuel combustion. Uric acid levels were lower in the smoker group of COPD patients (mean = 5.21 mg/dL), which indicates that oxidative stress is intensified with each cigarette smoked. Additionally, high concentrations of malondialdehyde were quantified for smoking patients diagnosed with COPD (mean = 2.72 µmol/L) compared to former smokers (mean = 2.43 µmol/L) and non-smoking (mean = 2.32 µmol/L) patients, which is another indicator of the implication of smoking in oxidative stress in COPD patients.
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Affiliation(s)
- Ioana Buculei
- Department of Biomedical Sciences, Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
- Doctoral School, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
| | - Mona Elisabeta Dobrin
- Medical Science Department, University of Medicine and Pharmacy, Iuliu Hațieganu, 400347 Cluj-Napoca, Romania
- Clinical Hospital of Pulmonary Diseases, 700115 Iasi, Romania
| | - Daniela Matei
- Department of Biomedical Sciences, Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
| | - Ilie Onu
- Department of Biomedical Sciences, Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
- Doctoral School of the Faculty of Chemical Engineering and Environmental Protection “Cristofor Simionescu”, Technical University “Gheorghe Asachi”, 700050 Iasi, Romania
| | - Cristina Vicol
- Department of Biomedical Sciences, Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
- Doctoral School, Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
| | - Ionel Bogdan Cioroiu
- Romanian Academy, Iași Branch, Research Center for Oenology, 700505 Iasi, Romania
| | - Marius Niculaua
- Romanian Academy, Iași Branch, Research Center for Oenology, 700505 Iasi, Romania
| | - Daniel Andrei Iordan
- Department of Individual Sports and Kinetotherapy, Faculty of Physical Education and Sport, “Dunărea de Jos” University of Galati, 800008 Galati, Romania
- Center of Physical Therapy and Rehabilitation, “Dunărea de Jos” University of Galati, 800008 Galati, Romania
| | - Andrei Cernomaz
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
| | - Antigona Carmen Trofor
- Clinical Hospital of Pulmonary Diseases, 700115 Iasi, Romania
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
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Zheng L, Pang Q, Xu H, Guo H, Liu R, Wang T. The Neurobiological Links between Stress and Traumatic Brain Injury: A Review of Research to Date. Int J Mol Sci 2022; 23:ijms23179519. [PMID: 36076917 PMCID: PMC9455169 DOI: 10.3390/ijms23179519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/17/2022] [Accepted: 08/21/2022] [Indexed: 11/16/2022] Open
Abstract
Neurological dysfunctions commonly occur after mild or moderate traumatic brain injury (TBI). Although most TBI patients recover from such a dysfunction in a short period of time, some present with persistent neurological deficits. Stress is a potential factor that is involved in recovery from neurological dysfunction after TBI. However, there has been limited research on the effects and mechanisms of stress on neurological dysfunctions due to TBI. In this review, we first investigate the effects of TBI and stress on neurological dysfunctions and different brain regions, such as the prefrontal cortex, hippocampus, amygdala, and hypothalamus. We then explore the neurobiological links and mechanisms between stress and TBI. Finally, we summarize the findings related to stress biomarkers and probe the possible diagnostic and therapeutic significance of stress combined with mild or moderate TBI.
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Affiliation(s)
- Lexin Zheng
- Department of Forensic Medicine, School of Basic Medicine and Biological Sciences, Soochow University, Suzhou 215123, China
| | - Qiuyu Pang
- Department of Forensic Medicine, School of Basic Medicine and Biological Sciences, Soochow University, Suzhou 215123, China
| | - Heng Xu
- Department of Forensic Medicine, School of Basic Medicine and Biological Sciences, Soochow University, Suzhou 215123, China
| | - Hanmu Guo
- Department of Forensic Medicine, School of Basic Medicine and Biological Sciences, Soochow University, Suzhou 215123, China
| | - Rong Liu
- Department of Forensic Medicine, School of Basic Medicine and Biological Sciences, Soochow University, Suzhou 215123, China
| | - Tao Wang
- Department of Forensic Medicine, School of Basic Medicine and Biological Sciences, Soochow University, Suzhou 215123, China
- Shanghai Key Lab of Forensic Medicine, Key Lab of Forensic Science, Ministry of Justice, China (Academy of Forensic Science), Shanghai 200063, China
- Correspondence:
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The Relationship between Oxidative Stress and Subjective Sleep Quality in People with Coronary Artery Disease. Brain Sci 2022; 12:brainsci12081070. [PMID: 36009133 PMCID: PMC9406162 DOI: 10.3390/brainsci12081070] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 07/25/2022] [Accepted: 08/05/2022] [Indexed: 12/02/2022] Open
Abstract
Background: (1) Sleep disorders are prevalent in coronary artery disease (CAD) patients and predict cardiac events and prognosis. While increased oxidative stress (OS) has been associated with sleep disorders, less is known about its relationship with sleep quality. Similarly, little is known of how this relationship might change with exercise, which can improve sleep quality. Factors of sleep quality, such as sleep duration and disturbances, are also important as they predict cardiovascular diseases better than a global score alone. This study investigated whether OS was associated with self-rated sleep quality and its factors before and after completing a 24-week exercise intervention. (2) Methods: CAD patients undergoing an exercise program were recruited. OS was measured at baseline by the concentrations of early- (lipid hydroperoxides, LPH) and late-stage (8-isoprostane, 8-ISO) lipid peroxidation products and their ratio. Sleep quality was measured by the self-reported Pittsburgh Sleep Quality Index (PSQI) instrument at baseline and termination. Three sleep factors—perceived sleep quality, sleep efficiency, and daily disturbances—were derived from the PSQI. (3) Results: Among CAD patients (n = 113, 85.0% male, age = 63.7 ± 6.4 years, global PSQI = 5.8 ± 4.0), those with poor sleep (PSQI ≥ 5) had higher baseline 8-ISO levels (F(1, 111) = 6.212, p = 0.014, ηp2 = 0.053) compared to those with normal sleep. Concentrations of LPH (F(1, 105) = 0.569, p = 0.453, ηp2 = 0.005) and 8-ISO/LPH ratios (F(1, 105) = 2.173, p = 0.143, ηp2 = 0.020) did not differ between those with poor sleep and normal sleep. Among factors, perceived sleep quality was associated with 8-ISO and 8-ISO/LPH, and daily disturbances were associated with 8-ISO. (4) Conclusions: A marker of late-stage lipid peroxidation is elevated in CAD patients with poor sleep and associated with daily disturbances, but not with other factors or with sleep quality and its factors after exercise intervention.
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N-acetylcysteine facilitates extinction of cued fear memory in rats via reestablishing basolateral amygdala glutathione homeostasis. Acta Pharmacol Sin 2022; 43:260-272. [PMID: 33927360 PMCID: PMC8791957 DOI: 10.1038/s41401-021-00661-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 03/16/2021] [Indexed: 02/03/2023]
Abstract
Individual differences in the development of uncontrollable fear in response to traumatic stressors have been observed in clinic, but the underlying mechanisms remain unknown. In the present study we first conducted a meta-analysis of published clinical data and found that malondialdehyde, an oxidative stress biomarker, was significantly elevated in the blood of patients with fear-related anxiety disorders. We then carried out experimental study in rats subjected to fear conditioning. We showed that reestablishing redox homeostasis in basolateral amygdale (BLA) after exposure to fear stressors determined the capacity of learned fear inhibition. Intra-BLA infusion of buthionine sulfoximine (BSO) to deplete the most important endogenous antioxidant glutathione (GSH) blocked fear extinction, whereas intra-BLA infusion of dithiothreitol or N-acetylcysteine (a precursor of GSH) facilitated extinction. In electrophysiological studies conducted on transverse slices, we showed that fear stressors induced redox-dependent inhibition of NMDAR-mediated synaptic function, which was rescued by extinction learning or reducing agents. Our results reveal a novel pharmacological strategy for reversing impaired fear inhibition and highlight the role of GSH in the treatment of psychiatric disorders.
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El Brouzi MY, Lamtai M, Zghari O, Ouakki S, Azizoun I, El Hessni A, Mesfioui A, Ouichou A. Intrahippocampal Effects of Nickel Injection on the Affective and Cognitive Response in Wistar Rat: Potential Role of Oxidative Stress. Biol Trace Elem Res 2021; 199:3382-3392. [PMID: 33230633 DOI: 10.1007/s12011-020-02457-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 10/21/2020] [Indexed: 02/07/2023]
Abstract
The present study focused on affective and cognitive behaviors in male Wistar rats, following direct and unique exposure to nickel chloride (NiCl2), as well as the possible involvement of oxidative stress. The rats were exposed to NiCl2 (300 μM), by intracerebral administration of 2 μL of this metal at the right hippocampus, using the stereotaxic approach. Five days after the surgery, a battery of behavioral tests was performed, including the open-field test (OFT) and elevated plus maze test (EPM) to assess the state of anxiety-like behavior and forced swimming test (FST) for depressive-like behavior. Y-maze and Morris Water Maze (MWM) were used to evaluate working memory and spatial learning. Thereafter, oxidative stress markers of the hippocampus were evaluated. The results confirm that NiCl2 exerts anxiogenic effects in both anxiety tests and depressogenic effects in the FST. In addition, MWM and Y-maze data show that NiCl2 causes memory and spatial learning disorders. The biochemical assay results showed that intrahippocampal injection of NiCl2 increased the levels of nitric oxide and lipid peroxidation (p < 0.001), while the activities of catalase and superoxide dismutase were significantly decreased in the hippocampus (p < 0.01). Overall, these results suggest that NiCl2 causes affective and cognitive disorders and oxidative stress in rats.
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Affiliation(s)
- Mohamed Yassine El Brouzi
- Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofaïl University, Kénitra, Morocco.
| | - Mouloud Lamtai
- Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofaïl University, Kénitra, Morocco
| | - Oussama Zghari
- Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofaïl University, Kénitra, Morocco
| | - Sihame Ouakki
- Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofaïl University, Kénitra, Morocco
| | - Ibrahim Azizoun
- Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofaïl University, Kénitra, Morocco
| | - Aboubaker El Hessni
- Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofaïl University, Kénitra, Morocco
| | - Abdelhalem Mesfioui
- Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofaïl University, Kénitra, Morocco
| | - Ali Ouichou
- Laboratory of Genetics, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofaïl University, Kénitra, Morocco
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Chen S, Lee J, Truong TM, Alhassen S, Baldi P, Alachkar A. Age-Related Neurometabolomic Signature of Mouse Brain. ACS Chem Neurosci 2021; 12:2887-2902. [PMID: 34283556 DOI: 10.1021/acschemneuro.1c00259] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Neurometabolites are the ultimate gene products in the brain and the most precise biomolecular indicators of brain endophenotypes. Metabolomics is the only "omics" that provides a moment-to-moment "snapshot" of brain circuits' biochemical activities in response to external stimuli within the context of specific genetic variations. Although the expression levels of neurometabolites are highly dynamic, the underlying metabolic processes are tightly regulated during brain development, maturation, and aging. Therefore, this study aimed to identify mouse brain metabolic profiles in neonatal and adult stages and reconstruct both the active metabolic network and the metabolic pathway functioning. Using high-throughput metabolomics and bioinformatics analyses, we show that the neonatal mouse brain has its distinct metabolomic signature, which differs from the adult brain. Furthermore, lipid metabolites showed the most profound changes between the neonatal and adult brain, with some lipid species reaching 1000-fold changes. There were trends of age-dependent increases and decreases among lipids and non-lipid metabolites, respectively. A few lipid metabolites such as HexCers and SHexCers were almost absent in neonatal brains, whereas other non-lipid metabolites such as homoarginine were absent in the adult brains. Several molecules that act as neurotransmitters/neuromodulators showed age-dependent levels, with adenosine and GABA exhibiting around 100- and 10-fold increases in the adult compared with the neonatal brain. Of particular interest is the observation that purine and pyrimidines nucleobases exhibited opposite age-dependent changes. Bioinformatics analysis revealed an enrichment of lipid biosynthesis pathways in metabolites, whose levels increased in adult brains. In contrast, pathways involved in the metabolism of amino acids, nucleobases, glucose (glycolysis), tricarboxylic acid cycle (TCA) were enriched in metabolites whose levels were higher in the neonatal brains. Many of these pathways are associated with pathological conditions, which can be predicted as early as the neonatal stage. Our study provides an initial age-related biochemical directory of the mouse brain and warrants further studies to identify temporal brain metabolome across the lifespan, particularly during adolescence and aging. Such neurometabolomic data may provide important insight about the onset and progression of neurological/psychiatric disorders and may ultimately lead to the development of precise diagnostic biomarkers and more effective preventive/therapeutic strategies.
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Affiliation(s)
- Siwei Chen
- Department of Computer Science, School of Information and Computer Sciences, University of California—Irvine, Irvine, California 92697, United States
- Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California—Irvine, Irvine, California 92697, United States
| | - Justine Lee
- Department of Pharmaceutical Sciences, School of Pharmacy, University of California—Irvine, Irvine, California 92697, United States
| | - Tri Minh Truong
- Department of Pharmaceutical Sciences, School of Pharmacy, University of California—Irvine, Irvine, California 92697, United States
| | - Sammy Alhassen
- Department of Pharmaceutical Sciences, School of Pharmacy, University of California—Irvine, Irvine, California 92697, United States
| | - Pierre Baldi
- Department of Computer Science, School of Information and Computer Sciences, University of California—Irvine, Irvine, California 92697, United States
- Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California—Irvine, Irvine, California 92697, United States
| | - Amal Alachkar
- Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California—Irvine, Irvine, California 92697, United States
- Department of Pharmaceutical Sciences, School of Pharmacy, University of California—Irvine, Irvine, California 92697, United States
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Filatova EV, Shadrina MI, Slominsky PA. Major Depression: One Brain, One Disease, One Set of Intertwined Processes. Cells 2021; 10:cells10061283. [PMID: 34064233 PMCID: PMC8224372 DOI: 10.3390/cells10061283] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/17/2021] [Accepted: 05/19/2021] [Indexed: 01/18/2023] Open
Abstract
Major depressive disorder (MDD) is a heterogeneous disease affecting one out of five individuals and is the leading cause of disability worldwide. Presently, MDD is considered a multifactorial disease with various causes such as genetic susceptibility, stress, and other pathological processes. Multiple studies allowed the formulation of several theories attempting to describe the development of MDD. However, none of these hypotheses are comprehensive because none of them can explain all cases, mechanisms, and symptoms of MDD. Nevertheless, all of these theories share some common pathways, which lead us to believe that these hypotheses depict several pieces of the same big puzzle. Therefore, in this review, we provide a brief description of these theories and their strengths and weaknesses in an attempt to highlight the common mechanisms and relationships of all major theories of depression and combine them together to present the current overall picture. The analysis of all hypotheses suggests that there is interdependence between all the brain structures and various substances involved in the pathogenesis of MDD, which could be not entirely universal, but can affect all of the brain regions, to one degree or another, depending on the triggering factor, which, in turn, could explain the different subtypes of MDD.
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12
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Nobis A, Zalewski D, Waszkiewicz N. Peripheral Markers of Depression. J Clin Med 2020; 9:E3793. [PMID: 33255237 PMCID: PMC7760788 DOI: 10.3390/jcm9123793] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 11/09/2020] [Accepted: 11/19/2020] [Indexed: 12/22/2022] Open
Abstract
Major Depressive Disorder (MDD) is a leading cause of disability worldwide, creating a high medical and socioeconomic burden. There is a growing interest in the biological underpinnings of depression, which are reflected by altered levels of biological markers. Among others, enhanced inflammation has been reported in MDD, as reflected by increased concentrations of inflammatory markers-C-reactive protein, interleukin-6, tumor necrosis factor-α and soluble interleukin-2 receptor. Oxidative and nitrosative stress also plays a role in the pathophysiology of MDD. Notably, increased levels of lipid peroxidation markers are characteristic of MDD. Dysregulation of the stress axis, along with increased cortisol levels, have also been reported in MDD. Alterations in growth factors, with a significant decrease in brain-derived neurotrophic factor and an increase in fibroblast growth factor-2 and insulin-like growth factor-1 concentrations have also been found in MDD. Finally, kynurenine metabolites, increased glutamate and decreased total cholesterol also hold promise as reliable biomarkers for MDD. Research in the field of MDD biomarkers is hindered by insufficient understanding of MDD etiopathogenesis, substantial heterogeneity of the disorder, common co-morbidities and low specificity of biomarkers. The construction of biomarker panels and their evaluation with use of new technologies may have the potential to overcome the above mentioned obstacles.
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Affiliation(s)
- Aleksander Nobis
- Department of Psychiatry, Medical University of Bialystok, pl. Brodowicza 1, 16-070 Choroszcz, Poland; (D.Z.); (N.W.)
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13
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Luan D, Zhao MG, Shi YC, Li L, Cao YJ, Feng HX, Zhang ZJ. Mechanisms of repetitive transcranial magnetic stimulation for anti-depression: Evidence from preclinical studies. World J Psychiatry 2020; 10:223-233. [PMID: 33134113 PMCID: PMC7582130 DOI: 10.5498/wjp.v10.i10.223] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/11/2020] [Accepted: 09/02/2020] [Indexed: 02/05/2023] Open
Abstract
This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies, including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway, anti-oxidative stress effects, enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway, increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway, and reducing the activity of the hypothalamic-pituitary-adrenocortical axis. We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning, shallow depth of stimulation, and difficulty in elucidating the neural circuit mechanism up- and down-stream of the stimulation target brain region.
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Affiliation(s)
- Di Luan
- Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ming-Ge Zhao
- Department of Nursing, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ya-Chen Shi
- Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ling Li
- Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Yu-Jia Cao
- Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Hai-Xia Feng
- Department of Nursing, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Zhi-Jun Zhang
- Department of Neurology, Affiliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Department of Psychology, Xinxiang Medical University, Xinxiang 453003, Henan Province, China
- Mental Health Center, Zhejiang University School of Medicine, Hangzhou 310013, Zhejiang province, China
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14
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Luduvico KP, Spohr L, Soares MSP, Teixeira FC, de Farias AS, Bona NP, Pedra NS, de Oliveira Campello Felix A, Spanevello RM, Stefanello FM. Antidepressant Effect and Modulation of the Redox System Mediated by Tannic Acid on Lipopolysaccharide-Induced Depressive and Inflammatory Changes in Mice. Neurochem Res 2020; 45:2032-2043. [PMID: 32500408 DOI: 10.1007/s11064-020-03064-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 05/19/2020] [Accepted: 05/27/2020] [Indexed: 12/24/2022]
Abstract
Depression is an emotional disorder that causes mental and physical changes, and has limited pharmacotherapy. Tannic acid (TA) is a polyphenol with previously described antioxidant and neuroprotective properties. The aim of this study was to evaluate the effects of TA on lipopolysaccharide (LPS)-induced depressive-like behavior, as well as oxidative stress parameters and TNF-α levels in the brains of mice. Animals were pretreated once daily, with TA (30 or 60 mg/kg), fluoxetine (20 mg/kg) or vehicle for 7 days. On the 7th day, the animals received a single injection of LPS (830 μg/kg). After 24 h, open field, forced swimming, tail suspension, and splash tests were conducted. The endotoxin induced depressive-like behavior in these mice and this was attenuated by TA. In the cerebral cortex, hippocampus, and striatum, LPS increased lipid peroxidation and reactive oxygen species production, and this was also prevented by TA administration. TA treatment also prevented a decrease in catalase activity within the striatum. Further, LPS administration caused increased levels of TNF-α in all brain structures, and this was prevented in the cortex by TA treatment. In conclusion, TA shows many neuroprotective properties, with demonstrated antioxidant, anti-inflammatory and antidepressant effects in this animal model of acute depressive-like behavior. Therefore, this compound could provide an alternative therapeutic approach for the treatment of depression.
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Affiliation(s)
- Karina Pereira Luduvico
- Programa de Pós-Graduação Em Bioquímica E Bioprospecção - Laboratório de Biomarcadores, Centro de Ciências Químicas, Farmacêuticas E de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, CEP: 96010-900, Brazil.
| | - Luiza Spohr
- Programa de Pós-Graduação Em Bioquímica E Bioprospecção - Laboratório de Neuroquímica, Inflamação E Câncer, Centro de Ciências Químicas, Farmacêuticas E de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, Brazil
| | - Mayara Sandrielly Pereira Soares
- Programa de Pós-Graduação Em Bioquímica E Bioprospecção - Laboratório de Neuroquímica, Inflamação E Câncer, Centro de Ciências Químicas, Farmacêuticas E de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, Brazil
| | - Fernanda Cardoso Teixeira
- Programa de Pós-Graduação Em Bioquímica E Bioprospecção - Laboratório de Neuroquímica, Inflamação E Câncer, Centro de Ciências Químicas, Farmacêuticas E de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, Brazil
| | - Alana Seixas de Farias
- Programa de Pós-Graduação Em Bioquímica E Bioprospecção - Laboratório de Biomarcadores, Centro de Ciências Químicas, Farmacêuticas E de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, CEP: 96010-900, Brazil
| | - Natália Pontes Bona
- Programa de Pós-Graduação Em Bioquímica E Bioprospecção - Laboratório de Biomarcadores, Centro de Ciências Químicas, Farmacêuticas E de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, CEP: 96010-900, Brazil
| | - Nathalia Stark Pedra
- Programa de Pós-Graduação Em Bioquímica E Bioprospecção - Laboratório de Neuroquímica, Inflamação E Câncer, Centro de Ciências Químicas, Farmacêuticas E de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, Brazil
| | | | - Roselia Maria Spanevello
- Programa de Pós-Graduação Em Bioquímica E Bioprospecção - Laboratório de Neuroquímica, Inflamação E Câncer, Centro de Ciências Químicas, Farmacêuticas E de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, Brazil
| | - Francieli Moro Stefanello
- Programa de Pós-Graduação Em Bioquímica E Bioprospecção - Laboratório de Biomarcadores, Centro de Ciências Químicas, Farmacêuticas E de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Pelotas, RS, CEP: 96010-900, Brazil.
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15
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Carvalho AF, Solmi M, Sanches M, Machado MO, Stubbs B, Ajnakina O, Sherman C, Sun YR, Liu CS, Brunoni AR, Pigato G, Fernandes BS, Bortolato B, Husain MI, Dragioti E, Firth J, Cosco TD, Maes M, Berk M, Lanctôt KL, Vieta E, Pizzagalli DA, Smith L, Fusar-Poli P, Kurdyak PA, Fornaro M, Rehm J, Herrmann N. Evidence-based umbrella review of 162 peripheral biomarkers for major mental disorders. Transl Psychiatry 2020; 10:152. [PMID: 32424116 PMCID: PMC7235270 DOI: 10.1038/s41398-020-0835-5] [Citation(s) in RCA: 105] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 04/03/2020] [Accepted: 05/01/2020] [Indexed: 01/03/2023] Open
Abstract
The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimer's disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.e., between-group meta-analyses) and that assessed biomarkers after treatment (i.e., within-group meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening cortisol levels in euthymic BD participants relative to controls and decreased pyridoxal levels in participants with schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral biomarkers for major mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a trans-diagnostic biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted.
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Affiliation(s)
- André F Carvalho
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
- Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada.
| | - Marco Solmi
- Neuroscience Department, University of Padova, Padova, Italy
- Neuroscience Center, University of Padova, Padova, Italy
- Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Marcos Sanches
- Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada
- Krembil Centre for NeuroInformatics, Toronto, ON, Canada
| | - Myrela O Machado
- Division of Dermatology, Women's College Hospital, Toronto, ON, Canada
| | - Brendon Stubbs
- Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK
- Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, UK
| | - Olesya Ajnakina
- Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Chelsea Sherman
- Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
| | - Yue Ran Sun
- Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
| | - Celina S Liu
- Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
| | - Andre R Brunoni
- Service of Interdisciplinary Neuromodulation, Laboratory of Neurosciences (LIM-27) and National Institute of Biomarkers in Psychiatry (INBioN), Department and Institute of Psychiatry, University of São Paulo, São Paulo, SP, Brazil
- Department of Internal Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Giorgio Pigato
- Neuroscience Department, University of Padova, Padova, Italy
- Neuroscience Center, University of Padova, Padova, Italy
| | - Brisa S Fernandes
- Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center, Houston, TX, USA
| | | | - Muhammad I Husain
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada
| | - Elena Dragioti
- Pain and Rehabilitation Centre, and Department of Medical and Health Sciences, Linköping University, SE-581 85, Linköping, Sweden
| | - Joseph Firth
- NICM Health Research Institute, Western Sydney University, Westmead, Australia
- Division of Psychology and Mental Health, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Theodore D Cosco
- Gerontology Research Center, Simon Fraser University, Vancouver, Canada
- Oxford Institute of Population Ageing, University of Oxford, Oxford, UK
| | - Michael Maes
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- IMPACT Strategic Research Center, Deakin University, Geelong, Australia
| | - Michael Berk
- IMPACT Strategic Research Center, Deakin University, Geelong, Australia
- Orygen, the National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia
- Centre for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia
- Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia
| | - Krista L Lanctôt
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada
- Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
| | - Eduard Vieta
- Psychiatry and Psychology Department of the Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain
| | - Diego A Pizzagalli
- Department of Psychiatry & McLean Hospital, Harvard Medical School, Belmont, MA, 02478, USA
| | - Lee Smith
- The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK
| | - Paolo Fusar-Poli
- Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
- OASIS Service, South London and Maudsley National Health Service Foundation Trust, London, UK
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - Paul A Kurdyak
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Canada Institute for Clinical Evaluative Sciences (ICES), Toronto, ON, Canada
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Michele Fornaro
- Department of Neuroscience, Reproductive Science and Dentistry, Section of Psychiatr, University School of Medicine Federico II, Naples, Italy
| | - Jürgen Rehm
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
- Campbell Family Mental Health Research Institute, CAMH, Toronto, Canada
- Addiction Policy, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
- Institute of Clinical Psychology and Psychotherapy & Center for Clinical Epidemiology and Longitudinal Studies, Technische Universität Dresden, Dresden, Germany
- Institute of Medical Science, University of Toronto, Toronto, Canada
- Department of International Health Projects, Institute for Leadership and Health Management, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Nathan Herrmann
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada
- Sunnybrook Research Institute, Toronto, ON, Canada
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16
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Visentin APV, Colombo R, Scotton E, Fracasso DS, da Rosa AR, Branco CS, Salvador M. Targeting Inflammatory-Mitochondrial Response in Major Depression: Current Evidence and Further Challenges. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:2972968. [PMID: 32351669 PMCID: PMC7178465 DOI: 10.1155/2020/2972968] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 02/26/2020] [Accepted: 03/17/2020] [Indexed: 02/07/2023]
Abstract
The prevalence of psychiatric disorders has increased in recent years. Among existing mental disorders, major depressive disorder (MDD) has emerged as one of the leading causes of disability worldwide, affecting individuals throughout their lives. Currently, MDD affects 15% of adults in the Americas. Over the past 50 years, pharmacotherapy, psychotherapy, and brain stimulation have been used to treat MDD. The most common approach is still pharmacotherapy; however, studies show that about 40% of patients are refractory to existing treatments. Although the monoamine hypothesis has been widely accepted as a molecular mechanism to explain the etiology of depression, its relationship with other biochemical phenomena remains only partially understood. This is the case of the link between MDD and inflammation, mitochondrial dysfunction, and oxidative stress. Studies have found that depressive patients usually exhibit altered inflammatory markers, mitochondrial membrane depolarization, oxidized mitochondrial DNA, and thus high levels of both central and peripheral reactive oxygen species (ROS). The effect of antidepressants on these events remains unclear. Nevertheless, the effects of ROS on the brain are well known, including lipid peroxidation of neuronal membranes, accumulation of peroxidation products in neurons, protein and DNA damage, reduced antioxidant defenses, apoptosis induction, and neuroinflammation. Antioxidants such as ascorbic acid, tocopherols, and coenzyme Q have shown promise in some depressive patients, but without consensus on their efficacy. Hence, this paper provides a review of MDD and its association with inflammation, mitochondrial dysfunction, and oxidative stress and is aimed at thoroughly discussing the putative links between these events, which may contribute to the design and development of new therapeutic approaches for patients.
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Affiliation(s)
| | - Rafael Colombo
- Instituto de Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, RS 95070 560, Brazil
| | - Ellen Scotton
- Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
- Programa de Pós-Graduação em Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Débora Soligo Fracasso
- Instituto de Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, RS 95070 560, Brazil
| | - Adriane Ribeiro da Rosa
- Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | - Catia Santos Branco
- Instituto de Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, RS 95070 560, Brazil
| | - Mirian Salvador
- Instituto de Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, RS 95070 560, Brazil
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17
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Syafrita Y, Amir D, Susanti R, Fadhilah I. Relationship of brain-derived neurotrophic factor, malondialdehyde, and 8-Hydroxy 2-Deoxyguanosine with post-ischemic stroke depression. Dement Neuropsychol 2020; 14:41-46. [PMID: 32206197 PMCID: PMC7077855 DOI: 10.1590/1980-57642020dn14-010007] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 12/21/2019] [Indexed: 12/22/2022] Open
Abstract
A few studies have shown that serum brain-derived neurotrophic factor (BDNF) level in post-stroke depression is highly correlated with memory and neuropsychiatric disturbances. OBJECTIVE This study aimed to elucidate the relationship of serum BDNF, malondialdehyde (MDA), and 8-Hydroxy 2-Deoxyguanosine (8-OhdG) levels in acute stroke cases with one-month post-stroke depression. METHODS An observational study was conducted of 72 post-ischemic stroke patients in the Neurology ward of the Dr. M. Djamil Hospital, Padang, West Sumatra, Indonesia. Acute stroke (< 48 hours) serum BDNF, MDA, and 8-OhdG levels were measured using ELISA. Based on observations using the Hamilton Depression Rating Scale conducted one month after stroke, respondents were divided into two groups: with and without depression. The mean serum level was analyzed using the t-test and Mann-Whitney test, while differences in basic characteristics were analyzed using the Chi-square test. Multivariate analysis was conducted to determine the most significant factor associated with post-stroke depression. The error rate was set at 5%. RESULTS BDNF levels in acute stroke were significantly lower in the depression group than in the non-depression group (p < 0.05). MDA and 8-OhdG levels in acute stroke were higher in the depression group (p < 0.05). BDNF level during acute stroke was negatively correlated with post-stroke depression, while, conversely, acute stroke MDA and 8-OhdG levels were positively correlated with depression. CONCLUSION BDNF had a negative correlation, while MDA and 8-OhdG had a positive correlation, with depression one-month post-stroke. 8-OhdG was the most influential factor in post-stroke depression.
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Affiliation(s)
- Yuliarni Syafrita
- Neurology Department, Faculty of Medicine, Andalas University,
Indonesia
| | - Darwin Amir
- Hospital, Perintis Kemerdekaan Street, Padang, West Sumatra,
Indonesia
| | - Restu Susanti
- Neurology Department, Faculty of Medicine, Andalas University,
Indonesia
| | - I Fadhilah
- Neurology Department, Faculty of Medicine, Andalas University,
Indonesia
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18
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Dowlati Y, Maheux M, Meyer JH. The Effect of Oral L-cysteine on Breast Milk and Plasma Cysteine Concentrations. Neuropsychiatr Dis Treat 2020; 16:3163-3172. [PMID: 33376332 PMCID: PMC7762443 DOI: 10.2147/ndt.s255205] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 09/19/2020] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Greater oxidative signaling is implicated in major depressive disorder; hence, there is considerable interest in developing oral supplements with anti-oxidant properties to prevent or treat mood disorders, such as postpartum depression. L-cysteine is a precursor for glutathione, an important antioxidant in the brain. So, developing L-cysteine as a dietary supplement may be useful, provided oral supplementation substantially raises its concentration in blood plasma yet does not affect its total concentration in breast milk. This study assessed the effect of oral L-cysteine on its concentration in breast milk and blood plasma of breastfeeding mothers. PARTICIPANTS AND METHODS Twenty-four health breastfeeding women were randomly assigned to 0, 1.5, or 3 g of oral L-cysteine. Free and total cysteine in breast milk; and free cysteine in plasma were measured. While breast milk is the gold standard, measurement of infant formulas provides indices of nutritional intake considered safe. Therefore, free cysteine was also measured in six different formulas. RESULTS Total cysteine in breast milk was not affected by oral L-cysteine (Repeated Measures of ANOVA (rANOVA), intervention effect: p=0.75). Free cysteine levels in breast milk did rise (rANOVA, intervention effect: p=0.017), but were within the range of common infant formulas. There was no significant effect of L-cysteine supplementation on free cysteine levels in plasma (rANOVA, intervention effect: p=0.25), although a post hoc analysis found a trend towards greater plasma cysteine 30 minutes after oral supplementation (t(14)=-1.69, p=0.11, 3g versus no-dose). CONCLUSION The negligible effect of oral cysteine administration on its total concentration in breast milk was favorable, but the minimal effect on its blood plasma concentration more strongly argues against further development of oral L-cysteine in postpartum, as well as other conditions.
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Affiliation(s)
- Yekta Dowlati
- CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada.,Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
| | | | - Jeffrey H Meyer
- CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada.,Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
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19
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Bohn T. Carotenoids and Markers of Oxidative Stress in Human Observational Studies and Intervention Trials: Implications for Chronic Diseases. Antioxidants (Basel) 2019; 8:E179. [PMID: 31213029 PMCID: PMC6616644 DOI: 10.3390/antiox8060179] [Citation(s) in RCA: 95] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 06/12/2019] [Accepted: 06/14/2019] [Indexed: 01/08/2023] Open
Abstract
Carotenoids include C30, C40 and C50 terpenoid-based molecules, many of which constitute coloured pigments. However, >1100 of these are known to occur in nature and only about a dozen are known to play a role in our daily diet. Carotenoids have received much attention due to their proposed health benefits, including reducing the incidence of chronic diseases, such as cardiovascular disease and diabetes. Many of these diseases are characterized by chronic inflammation co-occurring with oxidative stress, characterized by, for example, enhanced plasma F2-isoprostane concentrations, malondialdehyde, and 8-hydroxyguanosine. Though carotenoids can act as direct antioxidants, quenching, for example, singlet oxygen and peroxide radicals, an important biological function appears to rest also in the activation of the body's own antioxidant defence system, related to superoxide-dismutase, catalase, and glutathione-peroxidase expression, likely due to the interaction with transcription factors, such as nuclear-factor erythroid 2-related factor 2 (Nrf-2). Though mostly based on small-scale and observational studies which do not allow for drawing conclusions regarding causality, several supplementation trials with isolated carotenoids or food items suggest positive health effects. However, negative effects have also been reported, especially regarding beta-carotene for smokers. This review is aimed at summarizing the results from human observational studies/intervention trials targeting carotenoids in relation to chronic diseases characterized by oxidative stress and markers thereof.
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Affiliation(s)
- Torsten Bohn
- Department of Population Health, Luxembourg Institute of Health, L-1445 Strassen, Luxembourg.
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Filho PWLL, Chaves Filho AJM, Vieira CFX, Oliveira TDQ, Soares MVR, Jucá PM, Quevedo J, Barichello T, Macedo D, das Chagas Medeiros F. Peritoneal endometriosis induces time-related depressive- and anxiety-like alterations in female rats: involvement of hippocampal pro-oxidative and BDNF alterations. Metab Brain Dis 2019; 34:909-925. [PMID: 30798429 DOI: 10.1007/s11011-019-00397-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 02/06/2019] [Indexed: 12/12/2022]
Abstract
Endometriosis is a gynecological condition affecting 10% of women in reproductive age. High rates of depression and anxiety are observed in these patients. The mechanisms underlying endometriosis-induced behavioral alterations are still elusive. Animal models provide a useful tool to study the temporal sequence and biological pathways involved in this disease and comorbid states. Here, we sought to characterize time-related behavioral alterations in rats submitted to endometriosis model (EM) induced by peritoneal auto-transplantation of uterine tissues weekly for three weeks. Corticosterone stress reactivity, oxidative stress markers - reduced glutathione (GSH), lipid peroxidation, activity of superoxide dismutase (SOD) and myeloperoxidase (MPO) - and brain-derived-neurotrophic factor (BDNF) levels in the hippocampus were also evaluated. We observed a progressive increase in anxiety-like behavior from 14th to 21st days post-EM. Despair-like behavior was observed from the 14th day post-EM on, while anhedonia and apathetic-like behaviors accompanied by increased corticosterone stress response were detected on 21 days post-EM. Increased pain sensitivity was observed from the 7th day post-EM and was accompanied by increased endometrioma weight. The pro-oxidative alterations, decreased GSH and increased SOD activity were observed on 21 days post-EM, except for lipid peroxidation that was altered from the 14th day. Decreased BDNF also occurred on the 21st day. Therefore, this study demonstrates that EM is related to several features of clinical depression and proposes the contribution of hippocampal oxidative state and neurotrophic support for the emergence of these changes. Our results support the use of this model as a useful tool to test new strategies for endometriosis-related neuropsychiatric symptoms.
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Affiliation(s)
- Paulo Wagner Linhares Lima Filho
- Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000. CEP, Fortaleza, Ceará, 60430-270, Brazil
- Surgery Department, Faculty of Medicine, Universidade Federal do Ceará, Fortaleza, CE, Brazil
| | - Adriano José Maia Chaves Filho
- Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000. CEP, Fortaleza, Ceará, 60430-270, Brazil
| | - Charliene Freire Xavier Vieira
- Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000. CEP, Fortaleza, Ceará, 60430-270, Brazil
| | - Tatiana de Queiroz Oliveira
- Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000. CEP, Fortaleza, Ceará, 60430-270, Brazil
| | - Michelle Verde Ramo Soares
- Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000. CEP, Fortaleza, Ceará, 60430-270, Brazil
| | - Paloma Marinho Jucá
- Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000. CEP, Fortaleza, Ceará, 60430-270, Brazil
| | - Joao Quevedo
- Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
- Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
- Laboratory of Neurosciences, Graduate Program in Health Sciences, University of Southern Santa Catarina - UNESC, Criciúma, SC, Brazil
| | - Tatiana Barichello
- Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
- Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
- Laboratory of Neurosciences, Graduate Program in Health Sciences, University of Southern Santa Catarina - UNESC, Criciúma, SC, Brazil
| | - Danielle Macedo
- Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000. CEP, Fortaleza, Ceará, 60430-270, Brazil.
- National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, Brazil.
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Maes M, Bonifacio KL, Morelli NR, Vargas HO, Moreira EG, St Stoyanov D, Barbosa DS, Carvalho AF, Nunes SOV. Generalized Anxiety Disorder (GAD) and Comorbid Major Depression with GAD Are Characterized by Enhanced Nitro-oxidative Stress, Increased Lipid Peroxidation, and Lowered Lipid-Associated Antioxidant Defenses. Neurotox Res 2018; 34:489-510. [PMID: 29736827 DOI: 10.1007/s12640-018-9906-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Revised: 03/30/2018] [Accepted: 04/13/2018] [Indexed: 02/06/2023]
Abstract
Accumulating evidence shows that nitro-oxidative pathways play an important role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD) and maybe anxiety disorders. The current study aims to examine superoxide dismutase (SOD1), catalase, lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione (GSH), paraoxonase 1 (PON1), high-density lipoprotein cholesterol (HDL), and uric acid (UA) in participants with and without generalized anxiety disorder (GAD) co-occurring or not with BD, MDD, or tobacco use disorder. Z unit-weighted composite scores were computed as indices of nitro-oxidative stress driving lipid and protein oxidation. SOD1, LOOH, NOx, and uric acid were significantly higher and HDL and PON1 significantly lower in participants with GAD than in those without GAD. GAD was more adequately predicted by increased SOD + LOOH + NOx and lowered HDL + PON1 composite scores. Composite scores of nitro-oxidative stress coupled with aldehyde and AOPP production were significantly increased in participants with comorbid GAD + MDD as compared with all other study groups, namely MDD, GAD + BD, BD, GAD, and healthy controls. In conclusion, GAD is characterized by increased nitro-oxidative stress and lipid peroxidation and lowered lipid-associated antioxidant defenses, while increased uric acid levels in GAD may protect against aldehyde production and protein oxidation. This study suggests that increased nitro-oxidative stress and especially increased SOD1 activity, NO production, and lipid peroxidation as well as lowered HDL-cholesterol and PON1 activity could be novel drug targets for GAD especially when comorbid with MDD.
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Affiliation(s)
- Michael Maes
- Health Sciences Graduation Program, Health Sciences Center, State University of Londrina, Londrina, Parana, Brazil.
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
- Department of Psychiatry, Medical University of Plovdiv and Technological Center for Emergency Medicine, Plovdiv, Bulgaria.
- School of Medicine, IMPACT Strategic Research Centre, Deakin University, PO Box 281, Geelong, VIC, 3220, Australia.
| | - Kamila Landucci Bonifacio
- Health Sciences Graduation Program, Health Sciences Center, State University of Londrina, Londrina, Parana, Brazil
| | - Nayara Rampazzo Morelli
- Health Sciences Graduation Program, Health Sciences Center, State University of Londrina, Londrina, Parana, Brazil
| | - Heber Odebrecht Vargas
- Health Sciences Graduation Program, Health Sciences Center, State University of Londrina, Londrina, Parana, Brazil
| | | | - Drozdstoy St Stoyanov
- Department of Psychiatry, Medical University of Plovdiv and Technological Center for Emergency Medicine, Plovdiv, Bulgaria
| | - Décio Sabbatini Barbosa
- Health Sciences Graduation Program, Health Sciences Center, State University of Londrina, Londrina, Parana, Brazil
| | - André F Carvalho
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Centre for Addiction & Mental Health, Toronto, ON, Canada
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Hacimusalar Y, Eşel E. Suggested Biomarkers for Major Depressive Disorder. ACTA ACUST UNITED AC 2018; 55:280-290. [PMID: 30224877 DOI: 10.5152/npa.2017.19482] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 06/08/2017] [Indexed: 12/21/2022]
Abstract
Currently, the diagnosis of major depressive disorder (MDD) mainly relies on clinical examination and subjective evaluation of depressive symptoms. There is no non-invasive, quantitative test available today for the diagnosis of MDD. In MDD, exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment, and predicting the treatment response. In this article, it is aimed to review the findings of suggested biomarkers such as growth factors, cytokines and other inflammatory markers, oxidative stress markers, endocrine markers, energy balance hormones, genetic and epigenetic features, and neuroimaging in MDD and to evaluate how these findings contribute to the pathophysiology of MDD, the prediction of treatment response, severity of the disorder, and identification of subtypes. Among these, the findings related to the brain-derived neurotrophic factor, the hypothalamo-pituitary-adrenal axis, cytokines, and neuroimaging may be strong candidates for being biomarkers MDD, and may provide critical information in understanding biological etiology of depression. Although the findings are not sufficient yet, we think that the results of epigenetic studies will also provide very important contributions to the biomarker research in MDD. The availability of biomarkers in MDD will be an advancement that will facilitate the diagnosis of the disorder, treatment choices in the early stages, and prediction of the course of the disorder.
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Affiliation(s)
- Yunus Hacimusalar
- Department of Psychiatry, Kayseri Training and Research Hospital, Kayseri, Turkey
| | - Ertuğrul Eşel
- Department of Psychiatry, Erciyes University Faculty of Medicine, Kayseri, Turkey
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Islam MR, Islam MR, Ahmed I, Moktadir AA, Nahar Z, Islam MS, Shahid SFB, Islam SN, Islam MS, Hasnat A. Elevated serum levels of malondialdehyde and cortisol are associated with major depressive disorder: A case-control study. SAGE Open Med 2018; 6:2050312118773953. [PMID: 29770218 PMCID: PMC5946642 DOI: 10.1177/2050312118773953] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Accepted: 01/08/2018] [Indexed: 11/16/2022] Open
Abstract
Objectives: Major depressive disorder is diagnosed on the basis of patient’s self-reported experiences, behavior reported by relatives, and a mental status examination, and yet we do not have any reliable biomarker for this. Mood-regulating pathways are affected by oxidative injury to lipids and cortisol is released into the blood due to stimulation of corticotrophin receptors in the adrenal cortex. Here, we aimed to determine serum levels of malondialdehyde and cortisol in major depressive disorder patients and controls. Methods: We collected blood samples from 247 major depressive disorder patients and 248 controls. Serum levels of malondialdehyde and cortisol were measured by ultraviolet spectrophotometry and enzyme-linked immunosorbent assay kit, respectively. Results: We found malondialdehyde levels were significantly higher in patients than controls, with mean ± standard deviation at 4.49 ± 1.37 and 2.87 ± 0.82 µmol/L, respectively, p < 0.001. Cortisol levels were also found significantly higher in patients than controls, with mean ± SD at 19.22 ± 1.64 and 17.37 ± 1.34 µg/dL, respectively, p < 0.001. Significant negative correlation was observed between serum levels of malondialdehyde and cortisol in patients (r =−0.170, p = 0.021). Receiver operating characteristic analysis showed good diagnostic value for malondialdehyde and cortisol, with the area under the curve at 0.853 and 0.819, respectively. Conclusion: The present study suggests that increased serum levels of malondialdehyde and cortisol are strongly associated with major depressive disorder. We believe elevations of malondialdehyde and cortisol in serum level arise independently and they could serve as biomarkers for major depressive disorder.
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Affiliation(s)
- Md Rabiul Islam
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Md Reazul Islam
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Imtiaz Ahmed
- Department of Pharmaceutical Sciences, School of Health & Life Sciences, North South University, Dhaka, Bangladesh
| | | | - Zabun Nahar
- Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
| | - Mohammad Safiqul Islam
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali, Bangladesh
| | | | - Sheikh Nazrul Islam
- Institute of Nutrition and Food Science, University of Dhaka, Dhaka, Bangladesh
| | - Md Saiful Islam
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Abul Hasnat
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
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24
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Seyedsadjadi N, Berg J, Bilgin AA, Tung C, Grant R. Significant relationships between a simple marker of redox balance and lifestyle behaviours; Relevance to the Framingham risk score. PLoS One 2017; 12:e0187713. [PMID: 29107974 PMCID: PMC5673171 DOI: 10.1371/journal.pone.0187713] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 10/24/2017] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress has been closely linked to the progressive cell damage associated with emerging non-communicable disease (NCDs). Early detection of these biochemical abnormalities before irreversible cell damage occurs may therefore be useful in identifying disease risk at an individual level. In order to test this hypothesis, this study assessed the relationship between a simple measure of redox status and lifestyle risk factors for NCDs, and the population-based risk score of Framingham. In a cross-sectional study design, 100 apparently healthy middle-aged males (n = 48) and females (n = 52) were asked to complete a comprehensive lifestyle assessment questionnaire, followed by body fat percentage and blood pressure measurements, and blood collection. The ratio of plasma total antioxidant capacity to hydroperoxide (TAC/HPX) was used as an index of redox balance. One-way ANOVA and multiple linear regression analysis were performed to analyse the association between TAC/HPX, lifestyle components and other plasma biomarkers. The TAC/HPX ratio was higher in males compared to females (t96 = 2.34, P = 0.021). TAC/HPX was also lower in participants with poor sleep quality (t93 = 2.39, P = 0.019), with high sleep apnoea risk (t62.2 = 3.32, P = 0.002), with high caffeine (F(2, 93) = 3.97, P = 0.022) and red meat intake (F(2, 93) = 5.55, P = 0.005). These associations were independent of gender. Furthermore, the TAC/HPX ratio decreased with increasing body fat percentage (F(2, 95) = 4.74, P = 0.011) and depression score (t94 = 2.38, P = 0.019), though these associations were dependent on gender. Importantly, a negative association was observed between TAC/HPX levels and the Framingham risk score in both males (r(45) = -0.39, P = 0.008) and females (r(50) = -0.33, P = 0.019) that was independent of other Framingham risk score components. Findings from this study suggests that a relatively simple measure of redox balance such as the TAC/HPX ratio may be a sensitive indicator of redox stress, and may therefore serve as a useful biomarker for assessing an individual's specific NCD risk linked to unhealthy lifestyle practices.
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Affiliation(s)
- Neda Seyedsadjadi
- School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Jade Berg
- Australasian Research Institute, Sydney Adventist Hospital, Sydney, New South Wales, Australia
| | - Ayse A. Bilgin
- Department of Statistics, Macquarie University, Sydney, New South Wales, Australia
| | - Chin Tung
- Australasian Research Institute, Sydney Adventist Hospital, Sydney, New South Wales, Australia
| | - Ross Grant
- School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
- Australasian Research Institute, Sydney Adventist Hospital, Sydney, New South Wales, Australia
- Sydney Adventist Hospital Clinical School, University of Sydney, Sydney, New South Wales, Australia
- * E-mail:
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25
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Hennebelle M, Otoki Y, Yang J, Hammock BD, Levitt AJ, Taha AY, Swardfager W. Altered soluble epoxide hydrolase-derived oxylipins in patients with seasonal major depression: An exploratory study. Psychiatry Res 2017; 252:94-101. [PMID: 28259037 PMCID: PMC5611448 DOI: 10.1016/j.psychres.2017.02.056] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 02/10/2017] [Accepted: 02/24/2017] [Indexed: 12/19/2022]
Abstract
Many cytochrome p450-derived lipids promote resolution of inflammation, in contrast to their soluble epoxide hydrolase(sEH)-derived oxylipin breakdown products. Here we compare plasma oxylipins and precursor fatty acids between seasons in participants with major depressive disorder with seasonal pattern (MDD-s). Euthymic participants with a history of MDD-s recruited in summer-fall were followed-up in winter. At both visits, a structured clinical interview (DSM-5 criteria) and the Beck Depression Inventory II (BDI-II) were administered. Unesterified and total oxylipin pools were assayed by liquid chromatography tandem mass-spectrometry (LC-MS/MS). Precursor fatty acids were measured by gas chromatography. In nine unmedicated participants euthymic at baseline who met depression criteria in winter, BDI-II scores increased from 4.9±4.4 to 19.9±7.7. Four sEH-derived oxylipins increased in winter compared to summer-fall with moderate to large effect sizes. An auto-oxidation product (unesterified epoxyketooctadecadienoic acid) and lipoxygenase-derived 13-hydroxyoctadecadienoic acid also increased in winter. The cytochrome p450-derived 20-COOH-leukotriene B4 (unesterified) and total 14(15)-epoxyeicosatetraenoic acid, and the sEH-derived 14,15-dihydroxyeicostrienoic acid (unesterified), decreased in winter. We conclude that winter depression was associated with changes in cytochrome p450- and sEH-derived oxylipins, suggesting that seasonal shifts in omega-6 and omega-3 fatty acid metabolism mediated by sEH may underlie inflammatory states in symptomatic MDD-s.
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Affiliation(s)
- Marie Hennebelle
- Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA.
| | - Yurika Otoki
- Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA; Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi, Japan.
| | - Jun Yang
- Department of Entomology and Nematology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA.
| | - Bruce D Hammock
- Department of Entomology and Nematology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA.
| | - Anthony J Levitt
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
| | - Ameer Y Taha
- Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA.
| | - Walter Swardfager
- Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON Canada.
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26
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Ayers-Ringler JR, Oliveros A, Qiu Y, Lindberg DM, Hinton DJ, Moore RM, Dasari S, Choi DS. Label-Free Proteomic Analysis of Protein Changes in the Striatum during Chronic Ethanol Use and Early Withdrawal. Front Behav Neurosci 2016; 10:46. [PMID: 27014007 PMCID: PMC4786553 DOI: 10.3389/fnbeh.2016.00046] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Accepted: 02/26/2016] [Indexed: 01/03/2023] Open
Abstract
The molecular mechanisms underlying the neuronal signaling changes in alcohol addiction and withdrawal are complex and multifaceted. The cortico-striatal circuit is highly implicated in these processes, and the striatum plays a significant role not only in the early stages of addiction, but in the developed-addictive state as well, including withdrawal symptoms. Transcriptional analysis is a useful method for determining changes in gene expression, however, the results do not always accurately correlate with protein levels. In this study, we employ label-free proteomic analysis to determine changes in protein expression within the striatum during chronic ethanol use and early withdrawal. The striatum, composed primarily of medium spiny GABAergic neurons, glutamatergic and dopaminergic nerve terminals and astrocytes, is relatively homogeneous for proteomic analysis. We were able to analyze more than 5000 proteins from both the dorsal (caudate and putamen) and ventral (nucleus accumbens) striatum and identified significant changes following chronic intermittent ethanol exposure and acute (8 h) withdrawal compared to ethanol naïve and ethanol exposure groups respectively. Our results showed significant changes in proteins involved in glutamate and opioid peptide signaling, and also uncovered novel pathways including mitochondrial function and lipid/cholesterol metabolism, as revealed by changes in electron transport chain proteins and RXR activation pathways. These results will be useful in the development of novel treatments for alcohol withdrawal and thereby aid in recovery from alcohol use disorder.
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Affiliation(s)
| | - Alfredo Oliveros
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Graduate School, Mayo Clinic College of Medicine Rochester, MN, USA
| | - Yanyan Qiu
- Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Graduate School, Mayo Clinic College of Medicine Rochester, MN, USA
| | - Daniel M Lindberg
- Neurobiology of Disease PhD Program, Mayo Graduate School, Mayo Clinic Rochester, MN, USA
| | - David J Hinton
- Neurobiology of Disease PhD Program, Mayo Graduate School, Mayo Clinic Rochester, MN, USA
| | - Raymond M Moore
- Department of Biochemistry and Molecular Biology, Center for Individualized Medicine, Mayo Clinic Rochester, MN, USA
| | - Surendra Dasari
- Department of Health Sciences Research, Mayo Clinic College of Medicine Rochester, MN, USA
| | - Doo-Sup Choi
- Neurobiology of Disease PhD Program, Mayo Graduate School, Mayo ClinicRochester, MN, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Graduate School, Mayo Clinic College of MedicineRochester, MN, USA; Department of Psychiatry and Psychology, Mayo Clinic College of MedicineRochester, MN, USA
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